title: The neurotransmitter serotonin interrupts α-synuclein amyloid maturation.
abstract: Indolic derivatives can affect fibril growth of amyloid forming proteins. The neurotransmitter serotonin (5-HT) is of particular interest, as it is an endogenous molecule with a possible link to neuropsychiatric symptoms of Parkinson disease. A key pathomolecular mechanism of Parkinson disease is the misfolding and aggregation of the intrinsically unstructured protein α-synuclein. We performed a biophysical study to investigate an influence between these two molecules. In an isolated in vitro system, 5-HT interfered with α-synuclein amyloid fiber maturation, resulting in the formation of partially structured, SDS-resistant intermediate aggregates. The C-terminal region of α-synuclein was essential for this interaction, which was driven mainly by electrostatic forces. 5-HT did not bind directly to monomeric α-synuclein molecules and we propose a model where 5-HT interacts with early intermediates of α-synuclein amyloidogenesis, which disfavors their further conversion into amyloid fibrils.
authors.affiliation: Institute of Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria. fabio.falsone@uni-graz.at
authors.forename: S Fabio
authors.initials: SF
authors.lastname: Falsone
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.forename: Anita
authors.initials: A
authors.lastname: Karner
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Kungl
authors.forename: Simone
authors.initials: S
authors.lastname: Kosol
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
authors.forename: Klaus
authors.initials: K
authors.lastname: Zangger
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000682:Amyloid; D018377:Neurotransmitter Agents; D051844:alpha-Synuclein; D012701:Serotonin